CPNE1 Regulates The Proliferation Of Non-small Cell Lung Cancer Through C-MET

[Objective]To study the effect of CPNE1 on the proliferation of non-small cell lung cancer(NSCLC).To investigate whether CPNE1 affects the expression of c-MET and whether it regulates cell proliferation and induces drug resistance through c-MET.[Methods](1)Western blot was used to detect the expression of CPNE 1 and c-MET protein in non-small cell lung cancer cell lines.(2)HCC827 and A549 cell lines were selected as experimental objects according to the results of the above cell lines.CPNE1 overexpression cell lines were constructed by lentivirus technology,and CPNE1 interference cell lines were constructed by si-RNA interference technology.Western Blot and RT-PCR were used to detect the expression of CPNE1,and to determine whether the overexpressed and interfering cells were successfully constructed.(3)CCK8 and clone formation were used to detect the effect of CPNE1 on cell proliferation.(4)Western blot was used to detect the expression of p-MET and its downstream p-Akt and p-Erk signaling proteins.(5)The c-MET in CPNE1 overexpressing cell lines was interfered with by si-RNA technology,and the changes of p-Akt and p-Erk downstream were detected.(6)Addingdifferent concentrations of Capmatinib(MET inhibitor)and Gefitinib(EGFR-TKI)to lentivirus-mediated CPNE1 overexpresing cells and NC cells,IC50 was detected by CCK8.[Results]Overexpression of CPNE1 could enhance the proliferation of NSCLC cells,and interfering with CPNE1 could weaken the proliferation of NSCLC cells.Overexpression of CPNE1 can up-regulate p-MET,while interference of CPNE1 can down-regulate p-MET.In overexpressed cell lines,the up-regulation of p-MET was accompanied by the up-regulation of downstream p-Akt and p-Erk signals,while the change of p-Akt and p-Erk was weakened after the interference of MET.After adding MET inhibitor capmatinib,the growth of CPNE1 overexpressed cell was faster than that of control.The IC50 of capmatinib in CPNE1 overexpressed cell was 28.67,and the control was 10.56.The high expression of CPNE1 could make A549 cells resistant to capmatinib,but could not affect the sensitivity of HCC827 to gefitinib.[Conclusion]CPNE1 can promote the proliferation of non-small cell lung cancer through c-MET signaling pathway.In A549 cell line,the high expression of CPNE1 can reduce the sensitivity of cells to capmatinib and induce drug resistance.